Interleukin-6 (IL-6) is one of the principal mediators of the acute phase response and has important actions on early hematopoietic progenitors, hepatocytes, and on B- and T-lymphocytes. Excessive or inappropriate synthesis of IL-6 may be involved in the pathogenesis of rheumatoid arthritis and multiple myeloma. The objective of this work is to investigate the consequences of unregulated expression of IL-6 in normal lymphocytes, cell lines, and in intact animals. A series of retroviral vectors are being constructed that are capable of transferring the murine IL-6 coding sequence with the neomycin resistance gene, other growth factors with which IL-6 acts synergistically in vitro, and oncogenes implicated in the development of plasmacytomas. In addition, a modified retroviral vector with the murine immunoglobulin heavy chain enhancer replacing the Moloney viral enhancer element will be made with the objective of targeting the expression of these sequences to differentiating B-lymphocytes. These experiments should yield new information about the role of this cytokine in certain autoimmune and neoplastic disorders.